INHIBITION OF PRERETINAL PROLIFERATION BY FREE-RADICAL SCAVENGERS IN AN EXPERIMENTAL-MODEL OF TRACTIONAL RETINAL-DETACHMENT

An original model of experimental proliferative vitreoretinopathy cons isting of an intravitreal injection of 10(7) human platelets and 1 IU of hyaluronidase was developed in pigmented rabbits. One group of 11 e yes served as non-treated controls. Two other groups of 11 eyes each r eceived Ginkgo Biloba extracts which are known free radical scavengers (EGb761, Ipsen, France), given orally in two doses, 50 mg.kg(-1) day( -1) and 100 mg kg(-1) day(-1) respectively, from the day after the pla telet injection to the end of the first month. The fourth group (11 ey es) was intravenously injected with a unique dose of 15 000 U kg(-1) o f superoxide dismutase the day after platelet injection. All animals w ere ophthalmoscopically examined in a masked fashion twice a week for 1 month and killed at the end of the experiment for histological analy sis. Vitreoretinal proliferation was graded according to a six-stage c lassification. The non-treated eyes showed a high rate of retinal deta chment (11/11 eyes), with a mean final score of 3.91 +/- 0.94. Histolo gic examinations consistently showed retinal retraction by fibrocellul ar preretinal membranes spreading to both surfaces of the retina as we ll as preretinal neovascularization. Many cells positively reacted wit h anti-cytokeratin or anti-vimentin monoclonal antibodies. All three g roups of treated eyes showed significantly lower scores of vitreoretin al proliferation at almost each time point of examination. At the end of the study, five retinal detachments were found in the EGb761 group at 50 mg kg(-1) day(-1) (mean final score 2.45 +/- 1.37), only one in the group receiving 100 mg kg(-1) day(-1) (mean score 1.64 +/- 1.03), and one in the SOD treated eyes. The lowest mean score found at day 28 was observed in the group receiving SOD (1.36 +/- 1.43), although thi s group presented during the first 3 weeks with an intense vitreous an d sometimes anterior chamber inflammation. Statistical comparison betw een treatments did not show significant differences at most time point s of the study. These results demonstrate that antioxidants may effici ently prevent preretinal proliferation, in clinicopathological entitie s where free radicals had not yet been shown to play a direct pathogen etic role. They are also among the first attempts for inhibiting prere tinal proliferations with non-cytotoxic agents and using a non-ocular route.